Is trazodone (antidepressant) safe to use during pregnancy?

Trazodone Safety During Pregnancy

Trazodone can be used during pregnancy as available evidence does not show an increased risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. 1

Safety Profile in Pregnancy

• The FDA drug label indicates that published prospective cohort studies, case series, and case reports over several decades have not identified any drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes with trazodone use during pregnancy 1
• A 2023 comparative cohort study found no significant difference in the risk of major congenital anomalies between trazodone exposure (0.6%) and SSRI exposure (2.6%) during the first trimester 2
• Animal studies showed increased fetal resorption and other adverse effects at doses 7.3-11 times the maximum recommended human dose, but human data has not confirmed these risks 1

Pregnancy Registry Information

• Healthcare providers are encouraged to register pregnant patients taking trazodone in the National Pregnancy Registry for Antidepressants 1
• The estimated background risk of major birth defects in the general population is 2-4%, and miscarriage is 15-20% 1

Specific Pregnancy Outcomes

• A multicenter prospective controlled study found no statistically significant differences in rates of major malformations, spontaneous abortions, therapeutic abortions, gestational age at birth, or birth weight between women taking trazodone/nefazodone and control groups 3
• This study reported 121 (82.4%) live births, 20 (13.6%) spontaneous abortions, and 6 (4%) therapeutic abortions among 147 pregnancies with trazodone or nefazodone exposure 3
• Only 2 (1.6%) major malformations were observed among live births, which is within the baseline rate of 1-3% 3

Breastfeeding Considerations

• Data from published literature reports the transfer of trazodone into human milk 1
• Limited data from post-marketing reports have not identified an association of adverse effects on breastfed children 1
• A case study detected trazodone and its active metabolite in breast milk at concentrations of 50.2 and 3.2 ng/mL respectively, with no reported adverse effects in the infant at 1,3, and 6-month follow-ups 4

Potential Benefits in Pregnancy

• A randomized clinical trial found that trazodone treatment for insomnia during the third trimester reduced postpartum depression symptoms compared to placebo 5
• This suggests potential benefits for pregnant women suffering from insomnia, which affects approximately 15% of pregnant women 4

Clinical Recommendations

• Consider the risk of untreated depression when discontinuing or changing antidepressant medication during pregnancy 1
• For women requiring treatment for both depression and insomnia during pregnancy, bupropion may be considered as an alternative, as it does not seem to be associated with major congenital malformations or other significant adverse obstetrical outcomes 6
• Monitor the infant for potential adverse effects if continuing trazodone during breastfeeding, although reported adverse effects are rare 1, 4

Important Considerations

• The safety data, while reassuring, still has methodological limitations including small sample sizes and inconsistent comparator groups 1
• A systematic review noted that while no consistent evidence links trazodone to increased risks of congenital malformations, some studies suggested a possible association with increased risk of spontaneous and therapeutic abortions 7
• Further research with larger, well-controlled studies is needed to establish a more definitive safety profile 7, 2